Effects of central metformin administration on responses to air-jet stress and on arterial baroreflex function in spontaneously hypertensive rats.
OBJECTIVE
To examine effects of intracerebroventricular (ICV) administration of metformin on the responses to environmental stress and on arterial baroreflex function in conscious spontaneously hypertensive rats (SHR).


METHODS
SHR were instrumented with an ICV cannula and prepared for measurements of the mean arterial pressure (MAP), heart rate, and renal sympathetic nerve activity (RSNA) during air-jet stress (AJS). After recovery from a pretreatment AJS period, rats were allocated randomly to ICV administration of either vehicle (saline; n = 9) or 1 mg metformin (which is inactive dose after intravenous administration; n = 8). After stabilization for 1 h, the AJS was repeated. The arterial baroreflex control of the heart rate and RSNA was examined at the end of the experiment.


RESULTS
ICV metformin decreased the baseline heart rate (by 88+/-14 beats/min) and RSNA (by 19+/-8%) in the absence of changes in MAP. ICV vehicle did not affect responses to the AJS [change in MAP (deltaMAP) = +11+/-2 mmHg, change in heart rate (deltaHR) = +54+/-9 beats/min, change in RSNA (deltaRSNA) = +37+/-8%), but pressor, tachycardic, and renal sympathoexcitatory responses to the AJS were inhibited significantly by ICV metformin (deltaMAP = +4+/-3 mmHg, deltaHR = -5+/-5 beats/min; deltaRSNA = +11+/-3%). ICV metformin did not affect the arterial baroreflex range, but it did increase the maximal gain of the arterial baroreflex control of heart rate (-1.46+/-0.25 versus 0.67+/-0.13%/mmHg, P= 0.01) and RSNA (-5.04+/-1.10 versus -2.47+/-0.28%/mmHg, P = 0.053).


CONCLUSIONS
Central metformin administration attenuated the renal sympathoexcitatory response to environmental stress and increased the gain of the arterial baroreflex control of heart rate and RSNA. These actions may contribute to the antihypertensive effect of metformin.
Petersen
J S
JS
Department of Pharmacology, The Panum Institute, University of Copenhagen, Denmark.
DiBona
G F
GF
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001158:Arteries / Q000503:physiopathology*; D017704:Baroreflex / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D007276:Injections, Intraventricular; D007668:Kidney / Q000294:innervation; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000494:pharmacology; D010812:Physical Stimulation; D051381:Rats; D011918:Rats, Inbred SHR; D013312:Stress, Physiological / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology
D000959:Antihypertensive Agents; D008687:Metformin